Statins could hold key in battle against multiple sclerosis 

19/03/2014 00:00 
A cheap cholesterol lowering drug could give hope to patients with advanced multiple sclerosis (MS), according to a study published in The Lancet.
 
 

No treatments can currently abate the advanced stage of the disease, known as secondary progressive MS (SPMS), which gradually causes patients to become more disabled.
 
In a two-year clinical trial involving 140 patients with secondary progressive MS, researchers from UCLH and UCL found that the drug simvastatin slowed brain shrinkage, which is thought to contribute to patients’ impairments.
 
Supporting this finding, patients on simvastatin – a cholesterol lowering drug - achieved better scores on movement tests and questionnaires that assess disability than patients taking a placebo.
 
This research is an exciting breakthrough, as up until now successful clinical trials have mainly focused on treatments for the relapsing-remitting form of multiple sclerosis (RRMS).
 
Dr Jeremy Chataway, consultant neurologist at the National Hospital for Neurology and Neurosurgery was lead author on the paper. His work is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre.


He said: ‘In the progressive stage of MS the brain shrinks by about 0.6 per cent a year.
Our main measure of success was to reduce the rate of brain atrophy.


"Caution should be taken regarding over-interpretation of our brain imaging findings, because these might not necessarily translate into clinical benefit.


‘However, our promising results warrant further investigation in larger phase 3 disability-driven trials.


“The earlier, relapsing-remitting form of MS (RRMS), now has at least a dozen treatments after all the clinical trials over the last 20 years, but sadly for SPMS there are few disease modifying treatments. We hope this might be the start of finding an effective treatment for this stage of the disease.”
 
He added: “We were inspired to choose high dose simvastatin by a group in the US, in a trial for RRMS, which appeared to show some benefit.”
 
There are approximately 100,000 people in the UK with MS. At about 10-15 years into the disease, at least half will become secondary progressive, characterized by greater disability, and gradual worsening of the condition.  There are very few treatments that stop this worsening.
 
The drug simvastatin is usually used to lower cholesterol levels after heart attack and stroke. However there are downstream effects from the enzyme it blocks, which could theoretically improve blood vessel function or the entry of white blood cells into the central nervous system.
 
Researchers carried out a phase II proof of concept study to see the effect of high dosage on brain atrophy (shrinkage) in SPMS. Brain atrophy was measured using MRI (magnetic resonance imaging). The next step will be to see if the drug has a sustained effect on disability.
 
This study, developed and carried out over a seven-year period, used simvastatin at 80mg versus a dummy drug in 140 people with secondary progressive MS. The primary outcome was MRI based, focusing on brain atrophy. The rate of atrophy untreated is approximately 0.6% a year, which can be quantified over time using volumetric MRI.
 
Dr Chataway added: “We found the drugs were well tolerated, and that they reduced the rate of shrinkage by about 40%, which is really quite dramatic. There was also hints of an effect on disability, but as the trial was not powered with this in mind, this finding can only be described as exploratory.
 
“Although there was no immunological effects, simvastatin may have a vascular-protective role, and crucially perhaps, a neuroprotective role – as shown by reducing the rate of brain shrinkage. ”
 
The study provides an exciting platform that needs to be taken into a late phase III trial to see if the drug has a sustained effect on disability over a three-year period. Commenting on the possibilities of a phase III trial,

Dr Chataway said: “Simvastatin is an ideal candidate drug for treating secondary MS - not just because of the results of this study, and because of it’s well known safety profile, but also it is a re-purposed drug which may have a significant impact on reducing costs and increasing the chances of starting a phase III trial”.
  
Dean of the Faculty of Brain Sciences, UCL, Prof Alan Thompson added: “This is one of the first positive clinical trials for patients with secondary progressive MS and while a Phase III trial will be essential to confirm the results, it is a major contribution to the recent international initiative on progressive MS and complements the many other innovative studies being carried out by the MS team in central and east London under the auspices of MS@UCLP.”
 
The study was funded by J.P Moulton Foundation, Berkeley Foundation, Multiple Sclerosis Trials Collaboration, Rosetrees Trust and the National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre (BRC). 
 

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